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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allogeneic bone marrow transplantation is limited by the availability of suitable marrow donors and risk of graft-versus-host disease (GVHD) and opportunistic infection. In an attempt to ameliorate these limitations, umbilical cord blood has been postulated as an alternative source of allogeneic haemopoietic stem cells for transplantation. From September, 1994, umbilical cord blood from sibling donors has been used to reconstitute haemapoiesis in 44 children with acquired or congenital lympho-haemapoietic disorders, neuroblastoma, or metabolic diseases. Patients who had HLA-identical and HLA-1 antigen disparate grafts, had a probability of engraftment at 50 days after transplantation of 85%. No patient had late graft failure. The probability of grade II-IV GVHD at 100 days was 3% and the probability of chronic GVHD at one year was 6%. With a median follow-up of 1.6 years, the probability of survival for recipients of HLA-identical or HLA-1 antigen disparate grafts is 72%. We conclude that umbilical cord blood is a sufficient source of transplantable haemopoietic stem cells for children with HLA-identical or HLA-1 antigen disparate sibling donors with very low risk of acute or extensive chronic GVHD. The feasibility of umbilical-cord-blood transplantation with HLA-2 and HLA-3 antigen disparate sibling donors remains to be determined.
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PMID:Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease. 747 21

We have investigated whether retroviral mediated transfer of the IL-2 gene renders human neuroblastoma cells immunogenic, justifying their use in a clinical tumor immunization study. Fourteen neuroblastoma cell lines were established from patients with disseminated neuroblastoma and transduced with the vector G1Ncvl2, which contains the neomycin phosphotransferase gene and the cDNA of the human interleukin-2 gene. Clones secreting > 150 pg/10(6) cells/24 h of IL-2 were selected for further study. Secretion of IL-2 was maintained for at least 3 weeks in nonselective media, implying that production of the cytokine would continue under in vivo conditions. Co-culture of IL-2 transduced cell lines with patient lymphocytes induced potent cytotoxic activity against both transduced and parental neuroblastoma cell lines. This activity was HLA unrestricted, and predominantly mediated by CD16+ or CD56+ and CD8- lymphocytes. These data form the preclinical justification for our current immunization protocol for patients with relapsed or resistant neuroblastoma.
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PMID:Immunomodulatory effects of human neuroblastoma cells transduced with a retroviral vector encoding interleukin-2. 762 15

The reactivity of a mAb (M16) raised against a small cell lung carcinoma line is described. M16 identifies a surface antigen expressed on cells of neuroectodermal origin following activation, as well as neoplastic transformation. M16 antigen expression is increased on retinoblastoma and neuroblastoma cell lines upon 'in vitro' stimulation and it is induced 'in vivo' on glial cells activated following brain injury. Furthermore, glial tumors show levels of M16 molecule expression increasing with the degree of malignancy, and in a retinoblastoma cell line, the expression of M16 was inversely related to the level of HLA-Class I and N-CAM antigens. The M16 antigen may represent a marker of both activation and neoplastic progression for neuroectodermal cells.
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PMID:Biochemical characterization and membrane expression of an antigen shared by activated and neoplastic cells of neuroectodermal origin. 770 33

We have reviewed the causes and risk factors for early death in a group of 295 children who underwent any form of first bone marrow transplantation (BMT) between 1978 and 1992. The commonest indications for transplantation were acute lymphoblastic leukaemia 80 (27.1%), neuroblastoma 69 (23.3%), immune deficiency 57 (19.3%) and myeloid leukaemias/myelodysplasia 50 (16.9%). There were 120 (40.6%) allogeneic BMTs, 118 (40%) autologous BMTs, while 51 (17.2%) children usually with severe combine immune deficiency received BMT from a non-HLA-identical parent, sibling or other relative (FBMT). Two were from identical twins and four from matched unrelated donors (MUD). Thirty-three children (11.2%) died in the first 100 days; the main causes of death being infection (n = 5), relapse (n = 7), graft failure (n = 4), GVHD (n = 7) and organ failure with or without infection (n = 6). There was no significant change in the incidence of early deaths in the three successive 5 year periods (1978-82, 1983-87, 1988-92) although there was some shift in the causes. Infections were the commonest cause during the first 5 year period, relapses followed by GVHD in the second period and single organ failure followed by GVHD and infections in the third period. The main causes of early death were relapse after high-dose chemo/radiotherapy and autologous BMT (7 of 9 deaths) and GVHD and infection after allogeneic BMT (9 of 13 deaths). In the group of 51 children undergoing FBMT there were five deaths from infection, three from graft failure, one from organ failure and one from GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early deaths in children undergoing marrow ablative therapy and bone marrow transplantation. 771 76

Human T-lymphotropic virus type I (HTLV-I) is associated with a neurologic disease, HTLV-I-associated myelopathy-tropical spastic paraparesis, in which both pathological and immunological changes are observed within the central nervous system. The pathogenesis of infection in HTLV-I-associated myopathy-tropical spastic paraparesis is not well understood with respect to the cell tropism of HTLV-I and its relationship to the destruction of neural elements. In this study, neuroblastoma cells were infected with HTLV-I by coculturing with HUT-102 cells to demonstrate that cells of neuronal origin are susceptible to this retroviral infection. HTLV-I infection of the neuroblastoma cells was confirmed by verifying the presence of HTLV-I gp46 surface antigens by flow cytometry and by verifying the presence of HTLV-I pX RNA by Northern (RNA) blotting and in situ hybridization techniques. To determine whether HTLV-I infection could potentially lead to changes in cell surface recognition by the immune system, the infected neuroblastoma cells were analyzed for altered HLA expression. The HTLV-I-infected, cocultured neuroblastoma cells were shown, through cell surface antigen expression and RNA transcripts, to express HLA classes I and II. In contrast, cocultured neuroblastoma cells that did not become infected with HTLV-I expressed only HLA class I. HLA class I expression was enhanced by the cytokines tumor necrosis factor alpha and gamma interferon and in the presence of HUT-102 supernatant. In this system, expression of HLA class I and II molecules appeared to be regulated by different mechanisms. HLA class I expression was probably induced by cytokines present in the HUT-102 supernatant and was not dependent on HTLV-I infection. HLA class II expression required HTLV-I infection of the cells. The observation of HTLV-I infection leading to HLA induction in these neuroblastoma cells provides a possible mechanism for immunologic recognition of infected neuronal cells.
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PMID:Induction of HLA class I and class II expression in human T-lymphotropic virus type I-infected neuroblastoma cells. 790 13

We have attempted to distinguish in human neuroblastoma between the effects of mycN on differentiation and its potential to promote malignant progression. Others have observed out-growth of autocrine cells with evidence of an advanced malignant phenotype in a mycN-transfected clonal cell line derived from the single-copy mycN neuroblastoma, SK-N-SH. We have now transfected the parental cell line with the same mycN expression vector and selected 5 clones characterized by unique and stable chromosomal integration sites and variable exogenous copy numbers. mycN gene expression was variable in the different clones and correlated roughly with the copy number of transfected mycN genes. Clones with minimal levels of mycN gene expression had a neuroblastic phenotype and low numbers of surface HLA class-I molecules. Clones with high levels of mycN expression had a Schwann/glial-like phenotype with higher surface HLA class-I display without imbalance of expression of specific loci and accelerated growth. Two such clones were capable of anchorage-independent growth in the absence of serum, and acquired tumorigenic properties. Our results show that exogenous mycN expression can be associated with a differentiation of neuroblastoma cells along the Schwann/glial pathway and can induce accelerated and autonomous growth.
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PMID:Altered growth and phenotype in clonal mycN transfectants of the SK-N-SH neuroblastoma cell line. 792 94

Neuroblastoma is one of the commonest solid tumors in children. Conventional therapeutic approaches, such as surgery, chemotherapy and radiotherapy, fail to control tumor progression in stage III and IV patients. The search for novel therapeutic strategies should necessarily take into account immunotherapy and gene therapy. Here the theoretical bases for the development of such approaches are discussed. Studies carried out with neuroblastoma (NB) cell lines have shown that neoplastic cells express a wide array of potential tumor associated antigens (TAA) but are devoid of HLA molecules which are necessary for TAA presentation to the host immune system. Transfection of NB cells with the interferon gamma gene appears a promising approach, since this cytokine up-regulates the expression of class I HLA molecules in NB cells. Other cytokines of potential interest for gene transfer studies are interleukin 2 (IL2) and interleukin 12 (IL12).
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PMID:[Rational bases for new approaches to the therapy of pediatric solid tumors: immunotherapy and gene therapy]. 797 43

The first meeting devoted specifically to BMT in children took place on Hilton Head Island, SC, in March 1994 and included detailed reviews of the role of BMT in the management of diseases for which it has been a subject of considerable controversy: haemoglobinopathies (thalassaemia and sickle cell disease), metabolic storage disorders and neuroblastoma. The results of BMT using marrow donors other than HLA-identical siblings were presented, including data from a number of centres on the outcome in children transplanted from mismatched family donors. Experience of the collection and transplantation of alternative sources of haemopoietic stem cells in the paediatric age group has accumulated rapidly in recent years. The results of transplantation of peripheral blood stem cells and of umbilical cord blood stem cells indicate that both approaches may soon replace BMT as first-line treatment for some malignant and non-malignant disorders in children. While gene therapy offers exciting prospects for the future, it was discussed here principally as treatment for ADA deficiency and is likely to remain a more distant, although exciting, therapeutic option for many diseases currently treated by BMT.
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PMID:Bone marrow transplantation in children: current results and controversies.Meeting, Hilton Head Island, SC, March 1994. 799 32

Recombinant gamma-interferon (IFN-gamma) has recently been shown to be one of the most effective inducers of neuroblastoma (NB) cell differentiation. Since increasing evidence indicates that expression of MHC class-I and class-II antigens by tumour cells is important for immunorecognition and cell targeting, we tested whether induction of NB cell differentiation by IFN-gamma is followed by expression of HLA class-I and class-II molecules. LAN-5 human NB cell line completely lacks HLA class-I antigens. Their expression was induced in a dose-dependent manner by IFN-gamma. HLA class-II molecules are also absent on LAN-5 cells, but only DP antigens were dose-dependently induced by IFN-gamma, while DR and DQ molecules were unaffected by the treatment. To confirm and extend the immunological data to all the class-II molecules, we performed Northern blot analysis, observing that DP alpha mRNA was induced in a dose- and time-dependent manner. DO beta and DZ alpha genes were also induced peaking after 3 days of IFN-gamma treatment. DR beta and DQ beta genes, which were not induced by IFN-gamma, gave a normal pattern of enzyme restriction by Southern blot. To get an insight into the regulation of HLA class-II gene expression in the neuronal model, we measured the decline of the steady-state HLA class-II mRNA. DO beta mRNA rapidly returned to baseline level after removing IFN-gamma, while the decay rates of DP alpha and DZ alpha mRNA were very slow. This might indicate different regulation at the post-transcriptional level for DO beta mRNA with respect to DP alpha and DZ alpha mRNA. To strengthen these findings we evaluated the half-lives of the mRNA after IFN-gamma induction by means of actinomycin D treatment. HLA-DO beta mRNA had a shorter half-life, while DZ alpha and DP alpha had a longer decay rate. Finally, we report that treatment of LAN-5 cells with cycloheximide did not alter the rate of transcription of the HLA-DP alpha gene, suggesting that no protein factor(s) is/are needed to maintain DP alpha gene expression.
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PMID:Uncoordinate induction and differential regulation of HLA class-I and class-II expression by gamma-interferon in differentiating human neuroblastoma cells. 824 79

We report the toxicity and efficacy of a new conditioning regimen for bone marrow transplantation (BMT) in children with poor prognosis neuroblastoma (NBL). Twenty-seven patients with poor prognosis NBL were treated with teniposide (360 mg/m2) or etoposide (500 mg/m2), thiotepa (600-900 mg/m2), and 1200 cGy fractionated total body irradiation (fTBI) followed by autologous marrow rescue (n = 19) or allogeneic BMT from HLA-identical siblings (n = 8). The two patients who received teniposide, 600 mg/m2 thiotepa and fTBI had minimal toxicity but relapsed 4 and 12 months post-auto BMT. The next two patients received 750 mg/m2 thiotepa, 500 mg/m2 etoposide and TBI. They tolerated the conditioning regimen well and are alive and in remission 77 and 75 months post-BMT. At the next thiotepa dose level (900 mg/m2), the first two allograft recipients both experienced fatal regimen-related toxicity. All subsequent allograft recipients received 750 mg/m2 thiotepa and autograft recipients received 900 mg/m2 thiotepa. As of 1 April 1995, eight of the 19 patients who received autologous marrow are surviving disease-free 21 to 77 months post-BMT. Nine autograft recipients relapsed at 2 to 37 months following transplantation. One patient died of hepatic veno-occlusive disease 2 months after auto BMT, and one of pneumonia 6 months post-transplantation. Three allograft recipients have relapsed at 6, 10 and 39 months post-transplant and three are alive and in remission 75, 53 and 27 months post-BMT. Overall, 11/27 patients (41%) are alive and in remission 21-77 months (median 47 months) following BMT. A conditioning regimen consisting of 500 mg/m2 etoposide, thiotepa (750 mg/m2 for allograft recipients and 900 mg/m2 for autograft recipients) and 1200 cGy fTBI has acceptable toxicity and is at least as effective as melphalan-containing regimens in the treatment of high-risk NBL.
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PMID:A study of thiotepa, etoposide and fractionated total body irradiation as a preparative regimen prior to bone marrow transplantation for poor prognosis patients with neuroblastoma. 880 93


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